The pathology of sickle cell disease results from vasoocclusion caused by blockage of the microcirculation by non-deformable red cells filled with polymers of deoxy-hemoglobin S. The disease is characterized by chronic vasocclusive injury to several organs and acute events that include painful crises (which largely involves marrow infarct), acute chest syndrome, acute splenic sequestration, acute sickle liver, cerebral infarcts, renal papillary necrosis, femoral and humeral head necrosis, acute retinal vasoocclusion, and other manifestations. Finding objective criteria to evaluate risk factors and treatment protocols for sickle cell disease is a long-standing goal. To date, MRI of painful crisis has yielded results which are intriguing but difficult to evaluate. Detection of hypoxia may yield a useable marker. These experiments were designed to detect regions of hypoxia which may occur under ambient conditions in patients with sickle cell disease. The image intensity in T2 and T2* weighted images is influenced by the presence of deoxygenated hemoglobin because deoxygenated hemoglobin has a different magnetic susceptibility than oxygenated hemoglobin or tissue. The difference in magnetic susceptibility between the red cells and plasma and between the intra- and extravascular spaces results in more rapid loss of water proton transverse magnetization and ultimately results in reduced image intensity in spin-echo or gradient echo pulse sequences. The change in oxygen saturation in sickle cell patients in brain and bone marrow was investigated while the patient was breathing room air or high oxygen through a face mask and comparing the signal intensity changes in T2 or T2*-weighted images. These results were contrasted to results for normal human controls. A goal of these studies is to separate acute, ongoing events from the results of previous episodes of ischemia and fibrosis or expansion of hematopoietic tissue.